Defective CYP7B1 does not 7-hydroxylate 25OH-CHOL

Stable Identifier
Reaction [transition]
Homo sapiens
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25-hydroxycholesterol 7-alpha-hydroxylase (CYP7B1) normally 7alpha-hydroxylates 25-hydroxycholesterol (25OH-CHOL) to cholest-5-ene-3beta,7alpha,25-triol (CHOL3b,7a,25TRIOL). Defects in CYP7B1 can cause spastic paraplegia 5A, autosomal recessive (SPG5A; MIM:270800), a neurodegenerative disorder characterised by a slow, gradual, progressive weakness and spasticity of the lower limbs (Tsaousidou et al. 2008). Mutations causing SPG5A include S363F, G57R, R417H, F216S, Y275*, F470I, G87V and T297A (Tsaousidou et al. 2008, Schule et al. 2009, Goizet et al. 2009, Arnoldi et al. 2012). Defects in CYP7B1 can also cause congenital bile acid synthesis defect 3 (CBAS3; MIM:613812), a disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic CYP7B1 activity is undetectable (Setchell et al. 1998). A mutation causing CBAS3 is R388* (Setchell et al. 1998).
Literature References
PubMed ID Title Journal Year
18252231 Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration

Crosby, AH, Patel, H, Hentati, A, Lamont, PJ, Siddique, T, Simpson, MA, Laing, NG, Ouahchi, K, Hentati, F, Madrid, RE, Tsaousidou, MK, Patton, MA, Yang, Y, Warner, TT, Wilkinson, PA

Am. J. Hum. Genet. 2008
9802883 Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease

Thompson, HR, Sokol, RJ, Lathe, R, Russell, DW, Setchell, KD, Weslie Tyson, R, O'Connell, NC, Davis, DL, Schwarz, M, Lund, EG

J Clin Invest 1998
18855023 Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia

Crosby, AH, Brandt, E, Schöls, L, Klimpe, S, Karle, KN, Hübner, CA, Klebe, S, Tsaousidou, M, Schüle, R, Beetz, C, Deufel, T, Auer-Grumbach, M

Neurogenetics 2009
21214876 Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations

Musumeci, O, Martinuzzi, A, Scarlato, M, Crimella, C, Bresolin, N, Fantin, M, Toscano, A, D'Angelo, MG, Tenderini, E, Bassi, MT, Arnoldi, A

Clin. Genet. 2012
19439420 CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5

Tesson, C, Durr, A, Guimarães, J, Chinnery, PF, Mochel, F, Fontaine, B, Wendum, D, Goizet, C, Tsaousidou, M, Boukhris, A, Feki, I, Isidor, B, Forlani, S, Mhiri, C, Beetz, C, Guyant-Maréchal, L, Brice, A, Wolf, C, Chevy, F, Chazouillères, O, Stevanin, G, Coutinho, P, Crosby, A, Truchetto, J, Grid, D, Azulay, JP

Brain 2009
Catalyst Activity

oxysterol 7-alpha-hydroxylase activity of CYP7B1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP7B1 mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
hereditary spastic paraplegia DOID:2476 Hereditary spastic paraplegia, Hereditary spastic paraplegia, Hereditary spastic paraplegia (disorder), Hereditary spastic paraplegia, familial spastic paraplegia, HSMN V
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